Evaluation of the Effect of Magnesium Sulphate as Adjunct to Epidural Bupivacaine: An Institutional Based Study

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1 Original article: Evaluation of the Effect of Magnesium Sulphate as Adjunct to Epidural Bupivacaine: An Institutional Based Study RajulSubhash Karmakar 1, ShishirRamachandra Sonkusale 1* 1Associate Professor, Department of Anaesthesia, Dhanalakshmi Srinivasan Medical College & Hospital, Perambalur, Tamilnadu, India. *Corresponding author: Dr.Shishir Ramachandra Sonkusale, Associate Professor, Department of Anaesthesia, Dhanalakshmi Srinivasan Medical College & Hospital, Perambalur, Tamilnadu, India. Abstract Background: One of the safest and cost effective techniques is Epidural anaesthesia with the advantage of providing surgical anaesthesia and prolonged postoperative pain relief. Magnesium has antinociceptive properties due to its noncompetitive NMDA receptor antagonism, blocking ion channels in a voltagedependent fashion. Hence; the present study was plannedto assess the effect of magnesium sulphate as adjunct to epidural bupivacaine. Materials & Methods: The present study included assessment and comparison of effect of magnesium sulphate as adjuvant to epidural bupivacaine. A total of 48 patients scheduled to undergo lower abdominal and lower limb surgeries were included in the present study. All the patients were randomized into two study groups as follows: : included 24 patients who were given bupivacaine plus saline, Group B: included 24 patients who were given bupivacaine plus magnesium Assessment of sensory block was done bilaterally with the help of analgesia to pin prick with a short hypodermic needle in midclavicular line. Modified Bromage scale was used for evaluation of the motor blockage. All the results were analysed by SPSS software. Results: Time taken for achieving T6 block among the subjects of group A and group B was minutes and minutes respectively. Time to first epidural top-up for subjects of group A and group B was and minutes respectively. Commonly observed adverse reactions observed in the present study were Bradycardia, Hypotension, Nausea and vomiting, Sedation and Shivering. Conclusion: When magnesium sulphate is co-administered with bupivacaine, rapid onset of surgical anaesthesia is produced without any significant adverse effects. Key words: Bupivacaine, Magnesium Sulphate, Sensory. INTRODUCTION One of the safest and cost effective techniques is Epidural anaesthesia with the advantage of providing surgical anaesthesia and prolonged postoperative pain relief. It is also an effective treatment of operative pain blunts autonomic, somatic and endocrine responses. It has become a common practice to use polypharmacy approach for treatment of intra and postoperative pain, because no drug has yet been identified that specifically inhibits nociception without associated side effects. 1-3 To improve the quality of intraoperative anaesthesia, postoperative analgesia and aid early ambulation and recovery of motor block, several agents have been employed such as opioids and n-methyl d-aspartic acid (NMDA) receptor antagonists. The latter prevent central sensitisation induced by peripheral nociceptive stimulation by blocking dorsal horn NMDA receptor activation. Magnesium has antinociceptive properties due 364

2 to its non-competitive NMDA receptor antagonism, blocking ion channels in a voltagedependent fashion. 4-7 Hence; we planned the present study to assess the effect of magnesium sulphate as adjunct to epidural bupivacaine. MATERIALS & METHODS The present study was conducted in the Department of Anaesthesia, DhanalakshmiSrinivasan Medical College & Hospital, Perambalur, Tamilnadu, India. It included assessment and comparison of effect of magnesium sulphate as adjuvant to epidural bupivacaine. A total of 48 patients scheduled to undergo lower abdominal and lower limb surgeries were included in the present study. Inclusion criteria for the present study included: Patients between the age group of 20 to 55 years, Patients with absence of any known drug allergy, Patients with absence of any other systemic illness All the patients were randomized into two study groups as follows: : included 24 patients who were given bupivacaine plus saline, Group B: included 24 patients who were given bupivacaine plus magnesium Assessment of sensory block was done bilaterally with the help of analgesia to pin prick with a short hypodermic needle in midclavicular line. Modified Bromage scale was used for evaluation of the motor blockage (0: no motor block; 1: inability to raise extended legs; 2: inability to flex knees; 3: inability to flex ankle joints). 8 Haemodynamic response in all the patients was recorded. All the results were analysed by SPSS software. Chi- square test was used for assessment of level of significance. RESULTS In the present study, a total of 48 patients were analysed and were broadly divided into two study groups; group A and group B. Time taken for achieving T6 block among the subjects of group A and group B was minutes and minutes respectively. Time to first epidural top-up for subjects of group A and group B was and minutes respectively. Significant results were obtained while comparing the mean time required for achieving neuroaxial block landmarks in between the two study groups. Commonly observed adverse reactions observed in the present study were Bradycardia, Hypotension, Nausea and vomiting, Sedation and Shivering. No significant results were obtained while comparing the occurrence of adverse reactions in between the two study groups, except for occurrence of shivering. DISCUSSION In the present study, mean time taken for achieving T6 block among the subjects of group A and group B was minutes and minutes respectively. Time to first epidural top-up for subjects of group A and group B was and minutes respectively. Significant results were obtained while comparing the mean time required for achieving neuroaxial block landmarks in between the two study groups. Commonly observed adverse reactions observed in the present study were Bradycardia, Hypotension, Nausea and vomiting, Sedation and Shivering. No significant results were obtained while comparing the occurrence of adverse reactions in between the two study groups, except for occurrence of shivering. Yousef AA et al examined the effects of adding magnesium sulphate to epidural bupivacaine and fentanyl in patients undergoing elective caesarean section using combined spinal-epidural anaesthesia. Women ASA physical status I or II at term were recruited. All received 2 ml intrathecal 0.5% hyperbaric bupivacaine, 10 ml epidural 0.25% plain bupivacaine with fentanyl 100 µg, and were randomly allocated to receive either 10 ml of epidural 0.9% sodium chloride or

3 ml epidural 5% magnesium sulphate. The quality of surgical anaesthesia, incidence of hypotension, Apgar scores, intraoperative pain assessment, onset of postoperative pain, sedation scores and side effects were recorded in the postoperative period. The addition of magnesium to epidural bupivacaine and fentanyl in women undergoing elective caesarean section with combined spinal-epidural anaesthesia improved intraoperative conditions and the quality of postoperative analgesia. 9 Ghrab BE et al annualized 105 adult patients and randomly allocated them to one of three groups: (1) group Morphine (M): 10 mg of isobaric bupivacaine 0.5% (2 ml)+100 microg morphine (1 ml)+10 microg fentanyl (0.1 ml)+1 ml of isotonic saline solution, (2) group Magnesium (Mg): 10mg of isobaric bupivacaine 0.5% (2 ml)+100mg of magnesium sulphate 10% (1 ml)+10 microg fentanyl (0.1 ml)+1 ml of isotonic saline solution, (3) group Morphine+Magnesium (MMg): 10mg of isobaric bupivacaine 0.5% (2 ml)+100mg of magnesium sulphate 10% (1 ml)+100 microg morphine (1 ml)+10 microg fentanyl (0.1 ml). In patients undergoing caesarean section under spinal anaesthesia, the addition of Intrathecal morphine (IT) magnesium sulphate (100mg) to morphine 100 microg improved the quality and the duration of postoperative analgesia without increasing the incidence of adverse effects. 10 De Negri P et al compared the incidence of unwanted lower extremity motor blockade and the analgesic efficacy between small-dose (0.125%; 0.2 mg x kg(-1) x h(-1)) postoperative epidural infusions of bupivacaine (Group B; n = 28), levobupivacaine (Group L; n = 27), and ropivacaine (Group R; n = 26) in children after hypospadias repair. Motor blockade and pain were assessed at predetermined time points during 48 h by using a modified Bromage scale and the Children's and Infant's Postoperative Pain Scale (CHIPPS). Postoperative analgesia was almost identical in all three study groups (CHIPPS range, 0-3), with no need for the administration of supplemental analgesia in any patient. However, significantly more patients in Group B (n = 6; P = 0.03) displayed signs of unwanted motor blockade during the observation period compared with Group L (n = 0) and Group R (n = 0). In conclusion, significantly less unwanted motor blockade was associated with postoperative epidural infusions of 0.125% levobupivacaine or ropivacaine in children after hypospadias repair as compared with a similar infusion of bupivacaine. However, no difference with regard to postoperative analgesia could be detected among the three different local anesthetics studied. 11 Sakaguchi Y et al studied 90 ASA 1 or 2 patients scheduled for abdominal surgery under epidural anaesthesia, with or without general anaesthesia. Patients were randomly divided into two groups to receive a postoperative epidural infusion of fentanyl 5 micrograms/ml in bupivacaine 0.2%, with or without adrenaline 5 micrograms/ml, at a rate of 2 ml/h for more than 48 hours. Postoperative pain relief was assessed using visual analog scales (VAS), both at rest and during coughing, at 2, 24, and 48 hours after surgery. The number of rescue analgesics and side-effects such as nausea, vomiting, pruritus, respiratory depression, headache, muscle weakness, and hypotension were recorded. Patients who received adrenaline (n = 40) reported significantly lower mean VAS scores than those who received no adrenaline (n = 37), both at rest at 24 hours postoperatively and during coughing at 24 and 48 hours. The number of additional analgesics and incidence of side-effects did not differ between groups. In conclusion, the results of the present study demonstrate that the addition of adrenaline to a combination of fentanyl and bupivacaine improves the quality of epidural analgesia after abdominal surgery. Under the conditions of the study, they did not detect any disadvantage from the addition of adrenaline

4 CONCLUSION Under the light of above obtained data, the authors conclude that when magnesium sulphate is co-administered with bupivacaine, rapid onset of surgical anaesthesia is produced without any significant adverse effects. However; future studies are recommended. References 1. Chia YY, Liu K, Liu YC, Chang HC, Wong CS. Adding ketamine in a multimodal patient-controlled epidural regimen reduces post-operative pain and analgesic consumption. Anesth Analg. 1998;86: Roelants F. The use of neuxaxial adjuvant drugs (noeestigmine, clonidine) in obstetrics and gynaecological anaesthesia. Curr Opin Anaesthesiol. 2006;19: Lysakowsi C, Dumont L, Czarnetzki C, Trame MR. Magnesium as an adjuvant to postoperative analgesia: A systematic review of randomized trial. Anesth Analg. 2007;104: Goodman EJ, Haas AJ, Kantor GS. Inadvertent administration of magnesium sulphate through epidural catheter: report and analysis of a drug error. Int J Obstet Anesth 2006;15: Lejuste MJ. Inadvertent intrathecal administration of magnesium sulfate. S Afr Med J 1985;68: Mayer ML, Westbrook GL, Guthrie PB. Voltage-dependent block by magnesium of NMDA responses in spinal cord neurones. Nature 1984;309: Pockett S. Spinal cord synaptic plasticity and chronic pain. Anesth Analg 1995;80: Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Acta Aneaesthesiol Scand Suppl. 1965;75: Yousef AA1, Amr YM. The effect of adding magnesium sulphate to epidural bupivacaine and fentanyl in elective caesarean section using combined spinal-epidural anaesthesia: a prospective double blind randomised study. Int J Obstet Anesth Oct;19(4): doi: /j.ijoa Epub 2010 Sep Ghrab BE1, Maatoug M, Kallel N, Khemakhem K, Chaari M, Kolsi K, Karoui A. Does combination of intrathecal magnesium sulfate and morphine improve postcaesarean section analgesia?. Ann Fr Anesth Reanim May;28(5): doi: /j.annfar Epub 2009 May De Negri P1, Ivani G, Tirri T, Modano P, Reato C, Eksborg S, Lonnqvist PA. A comparison of epidural bupivacaine, levobupivacaine, and ropivacaine on postoperative analgesia and motor blockade. Anesth Analg Jul;99(1): Sakaguchi Y1, Sakura S, Shinzawa M, Saito Y. Does adrenaline improve epidural bupivacaine and fentanyl analgesia after abdominal surgery? Anaesth Intensive Care Oct;28(5):

5 Parameter Number of subjects Mean age (years) Males Females Table 1: Demographic details of the patients Group B Graph1: Time duration for achieving neuroaxial block landmarks Group B Time taken for achieving T6 block (minutes) Time to first epidural top-up (minutes) Adverse reaction Bradycardia Hypotension Nausea and vomiting Sedation Shivering *: Significant Table 2: Comparison of adverse reactions Group B P- value * 368